The invention concerns test elements, in particular diagnostic test elements, for determining the presence or concentration of biological, medical or biologically or medically effective substances including nucleic acids, proteins, viruses, microorganisms and cells, characterized in that these test elements contain nanofibers.
Diagnostic test elements, and in particular, test strips, contain a wide variety of fiber-based materials. Papers or fleeces are especially noteworthy. Fleeces in particular are used to separate undesired sample components. As an example, reference is made to blood separation fleeces in glucose tests or in the test strips from, e.g., the Reflotron® system. The fibers that are used in papers or fleeces of the prior art are characterized by diameters between about 5 μm and 200 μm.
Nanofibers have been basically known since about 1930. They are produced by the so-called electrospinning process in which a thin fiber is produced by applying a high voltage in the range of 10-55 kV to a droplet of a polymer solution or polymer melt (Formhals, A., U.S. Pat. Nos. 1,975,504; 2,160,962; 2,187,306).
Nanofibers have extremely small diameters. Fibers having diameters of 10-2000 nm are obtainable depending on the material. In some cases branched fibers are obtained or fibers are obtained which contain a variable number of polymer beads which can be of different sizes on the fibers. Important influencing variables are known to a person skilled in the art or may be found in the pertinent literature (e.g., Li and Xia, Adv. Matter. 16 (2004), 1151-1170).
The use of nanofibers in medical products is described in U.S. Publication No. 2003/0171053. This publication concerns a medical device which is covered with a nanofiber layer in order to improve biocompatibility. Other publications relate to a brain probe which is coated with nanofibers to improve the biocompatibility and measuring stability (e.g., U.S. Publication No. 2002/0106496 or DiPaolo et al., Proc. 2nd Joint EMBS/BMES Conf. Houston Tex., USA, 23-23, October 2002).
U.S. Publication No. 2003/0217928 discloses a process for the electrosynthesis of nanostructures which can be used to detect an analyte also within an electrically conductive array.
WO 02/40242 describes a process for producing products for medical and cell-biological use, e.g., stents by electrospinning nanofibers based on collagen.
WO 03/026532 describes the use of nanofibers for medical devices, for example, balloons, catheters, filters and stents.
WO 03/087443 discloses a process for applying nanofibers to an object, for example medical devices such as stents, or devices for the controlled release of drugs.
Feng et al. (Angew. Chem. Int. Ed. 42 (2003), 800-802) and Feng et al. (Angew. Chem. Int. Ed. 41 (2002), 1221-1223) describe the production of “superhydrophobic” surfaces made of short nanofibers.
The use of fibers of the usual diameter in test elements for diagnostic applications has specific disadvantages, especially relating to the separation of blood cells. The fiber matrices in known test elements typically have relatively coarse, non-uniform porosity. Blood cells are either not retained by the large pores or they are retained in the interior of a fabric layer or fleece. The large pores cause lysis due to the high capillarity or due to injury or rupture of the membrane of red blood corpuscles on sharp corners and edges, especially in the case of glass fiber fleeces. Another disadvantage of fleeces or fabrics of the prior art is that these materials become relatively thick and retain correspondingly large volumes of liquid in the interstitial space of the fibers. This is problematic in the context of the development trend towards smaller and smaller sample volumes.
Structures made of hydrophobic conventional fibers can be used as liquid barriers. Examples of these are known under the trade name Tyvek®. However, a disadvantage of these structures is that an aqueous solution which comes into contact with these fabrics rolls off the surface, which is why they are not able to penetrate into the pores.